OBJECTIVES: To formulate crosslinker-modified etchants with phosphoric acid (PA) and an organic acid for effective dentin demineralization while addressing solubility issues, and to evaluate their impact on bond strength, nanoleakage, and matrix metalloproteinases (MMP) activity in sound dentin (SD) and caries-affected dentin (CAD) before and after thermocycling. 

METHODS: Crosslinker-modified etchants were prepared by mixing 35% tartaric acid (TA) and 10% PA and adding 1% of theaflavins (TF), cranberry extract (CR), or EDC/NHS (EDC). The etchants without crosslinker were used as controls. Dentin surfaces of 74 human molars were exposed, and 35 of them were submitted to a microbiological cariogenic challenge to create CAD. Specimens from SD and CAD were randomly allocated into 10 groups according to the different etchants. Resin-dentin interfacial bonding properties were evaluated after 24h and after 10,000 thermocycling through microtensile bond strength (mcTBS), nanoleakage and MMPs activity via in situ zymography. Statistical analysis was performed using ANOVA followed by Games-Howell or Tukey's tests.

RESULTS: Compared to the control and EDC-modified groups, TF- and CR-modified etchants maintained stable bond strength and significantly reduced MMP activity, preserving this protection even after thermocycling, which simulates one year of clinical aging, regardless of dentin type (both SD and CAD). While their impact on nanoleakage in CAD was less pronounced after thermocycling, it remained below 50% of the levels observed in the control and EDC-modified groups.

SIGNIFICANCE: Crosslinker-modified etchants, particularly TF and CR, provide a promising approach for simultaneous etching and biomodification of clinically relevant dentin substrates, enhancing bonding durability.

Background: The Indian subcontinent has the highest incidence and prevalence of Oral Squamous cell carcinoma. Recently, there has been a shift in paradigm favoring natural products to combat cancer, owing to the high costs and immense side effects associated with the conventional treatments such as surgery, radiotherapy, and chemotherapy. Cancer statistics express that consumption of diets rich in fresh fruits and vegetables is inversely associated with cancer incidence. The same has led to the increased number of studies in this area in recent times. The cytotoxic effect of many fruit extracts on various cancers, like cervical cancer, breast cancer, and colon cancer, has been reported. 

Aim: To evaluate the cytotoxic effect of Vaccinium macrocarpon (cranberry) and Punica granatum (pomegranate) extracts on oral cancer cell lines. 

Materials and Methods: Ethanolic extract of Punica granatum pericarp, fruit, and Vaccinium macrocarpon fruit were prepared. Oral cancer (KB) cell line was procured and cultured. Anti- proliferative assay (MTT assay) was performed with various concentrations of all three fruit extracts on oral cancer. Percentage of cell viability for each concentration was calculated, and the half maximal inhibitory concentration (IC50) was derived for the extracts. The role of apoptosis in the cytotoxicity of these extracts was assessed by analysing DNA fragmentation via gel electrophoresis. The data obtained was analysed using Pearson's correlation. 

Results: The study revealed a significant decrease in the percentage of viable cells with increasing concentration of the extract. The IC50 value of Punica granatum pericarp, fruit, and Vaccinium macrocarpon extract was 5.625 mu g/mL, 15 mu g/mL, and 27.5 mu g/mL, respectively. On comparison, Punica granatum pericarp extract showed the highest anti-carcinogenic activity. The DNA fragmentation assay showed a DNA laddering pattern, indicative of apoptosis, in the cells treated with Punica granatum pericarp extract. 

Conclusion: Punic granatum pericarp, fruit, and Vaccinium macrocarpon exhibited sufficient anticancer activity against oral cancer (KB) cells. Apoptosis was shown to play a role in the cytotoxic effect of Punica granatum pericarp extract against oral cancer cells.

Background/Objectives: Low-grade inflammation and microbial imbalance have been thought to play a role in the pathogenesis of Symptomatic Uncomplicated Diverticular Disease (SUDD). We aimed to assess the efficacy of a cranberry formulation in reducing the inflammatory state of the colon and symptoms in SUDD patients. 

Methods: Twenty patients were enrolled in a prospective, multi-center, open-label, pilot study. We enrolled SUDD patients in whom fecal calprotectin (FC) was assessed at baseline and during the follow-up, with a baseline value ≥ 50 µg/g. Patients were treated with a gastroresistant formulation of cranberry (Vaccinium macrocarpon), one tablet/day for 4 weeks, followed by an 8-week observation period. The primary endpoint was to assess the efficacy of this gastroresistant cranberry formulation in reducing the inflammatory state of the colon by FC assessment. The secondary main endpoint was to assess the impact of this formulation on SUDD symptoms (assessed by the Visual Analog Scale, VAS). Intention-to Treat (ITT) and Per-Protocol (PP) analyses were performed. 

Results: At baseline, the mean FC value was 110 ± 118 μg/g; it was 72 ± 24 μg/g and 82 ± 19 μg/g after 4 weeks of treatment, and after a further 8 weeks of observation, it was significantly reduced on both ITT (p = 0.0001) and PP (p = 0.001). About the secondary main endpoint (namely symptoms of SUDD), the mean values according to the VAS were reduced significantly both at the end of the treatment and after 8 weeks post treatment. 

Conclusions: This gastroresistant formulation of cranberry may be able to reduce inflammation and symptoms in SUDD patients. Furthermore, large studies have to confirm these preliminary and promising results.

Gentamicin (GTC) is a widely used aminoglycoside antibiotic, but its therapeutic application is limited by nephrotoxic and hepatotoxic effects primarily driven by oxidative stress. This study investigated the potential protective role of cranberry (CRB) (Vaccinium macrocarpon), known for its antioxidant and anti-inflammatory properties, against GTC-induced nephrotoxicity in rats. Hepatic biochemical and histopathological parameters were also evaluated as supportive markers of systemic toxicity. Thirty-two rats were divided into four groups: Control, CRB, GTC + CRB, and GTC. GTC (80 mg/kg, s.c.) and CRB (200 mg/kg, p.o.) were administered for seven consecutive days. Biochemical analyses showed significant increases in serum BUN, urea, creatinine, ALT, and AST levels in the GTC group, confirming renal and hepatic impairment. Co treatment with CRB reduced these elevations and improved antioxidant parameters, reflected by decreased MDA and oxidative stress index levels and increased total and native thiols (p < 0.001). Gene expression analyses demonstrated that GTC upregulated pro-apoptotic genes (Bax, caspase-3, -9) and downregulated the anti-apoptotic Bcl-2, whereas CRB co-administration reversed these alterations. Histopathological evaluations supported the biochemical findings, revealing severe tubular and hepatocellular necrosis, inflammatory infiltration, and hemorrhage in the GTC group, which were markedly alleviated by CRB supplementation. These results suggest that CRB may exert a partial renoprotective effect against GTC-induced oxidative and apoptotic damage, possibly through its antioxidant and cytoprotective properties.

The search has been ongoing for safe and effective antimicrobial agents for control and prevention of oral biofilm associated with disease. Clinical trials for oral specific anti-bacterials are costly and often provide inconclusive results. The simple approach of ex vivo testing of these agents has not demonstrated utility, likely due to variability of effects observed even with a single donor. We show how shed oral biofilms, easily obtained from donor saliva, and tested under optimized conditions, respond reproducibly to anti-bacterial challenges measured by reductions in rRNA accumulation in susceptible taxa. Responses are in part donor specific, but many bacteria taxa were shown to be reproducibly susceptible over a group of donors. For two antibiotics, vancomycin and penicillin G tested at pharmacologic levels, a subset of Gram-positive bacteria was inhibited. A natural product with antibacterial properties, diluted Vaccinium macrocarpon (cranberry) juice, was shown to inhibit a range of oral taxa, including Alloprevotella sp__HMT_473, Granulicatella adiacens, Lachnoanaerobaculum umeaense, Lepotrichia sp__HMT_215, Peptostreptococcus stomatis, Prevotella nanceiensis, Stomatobaculum sp__HMT_097, Veillonella parvula, and kill some targets. The model discussed in this study has promise as a rapid, precise, and reproducible ex vivo method to test and identify potential clinically useful antimicrobial agents active against the oral biofilm community.

Objectives: Despite the increasing scientific evidence regarding the application of Cranberries in dentistry, a comprehensive understanding of their potential benefits, active constituents, and mechanisms of action remains lacking. Consequently, this narrative review aims to meticulously analyze and consolidate the existing scientific literature on the utilization of Cranberries for the prevention and treatment of oral diseases. 

Materials and Methods: Electronic databases (PubMed, Scopus, and Web of Science) were searched up to October 2025. This review included in vitro, in vivo, and clinical research studies. A two-phase selection process was carried out. In phase 1, two reviewers independently screened titles and abstracts to identify potentially eligible studies. In phase 2, the same reviewers performed the full-text assessments of the eligible articles. 

Results: Among the 93 eligible articles, most assessed Cranberry use in Cariology (n = 28) and Periodontics (n = 26). Biofilm and microbial virulence factors (n = 46) were the most frequently studied topics. Cranberry extract (n = 32) and high-molecular-weight non-dialyzable material (NDM) (n = 23) were the most evaluated Cranberry fractions. Overall, Cranberry-derived compounds were identified as non-toxic and demonstrated promising antimicrobial activity against dental caries-related microorganisms in preclinical studies (n = 20). Regarding periodontal and peri-implant diseases, Cranberry demonstrated host immune modulator effects, counteracting the inflammatory and destructive mechanisms (n = 8). Additionally, Cranberries presented benefits in reducing the inflammation associated with periodontal disease and temporal mandibular joint lesions (n = 1). Regarding dental erosion, Cranberry inhibited dentin erosion (n = 4); however, no effect was observed on enamel lesions (n = 2). As an antioxidant agent, Cranberry showed effectiveness in preventing dental erosion (n = 18). Beyond that, Cranberry neutralized reactive oxygen species generated immediately after dental bleaching, enhancing bond strength (n = 2) and counteracting the oxygen ions formed on the tooth surface following bleaching procedures (n = 3). In osteoclastogenesis assays, A-type proanthocyanidins inhibited bone resorption (n = 1). In osteogenic analysis, preservation of hydroxycarbonate apatite deposition and an increase in early and late osteogenic markers were observed (n = 2). 

Conclusions: Cranberry bioactive compounds, both individually and synergistically, exhibit substantial potential for diverse applications within dentistry, particularly in the prevention and management of oral and maxillofacial diseases. This review provides insights into the plausible incorporation of Cranberries in contemporary dentistry, offering readers an informed perspective on their potential role.

The increasing resistance of microorganisms to currently used antimicrobials requires the urgent development of new effective treatments. Plant-based natural products can be an alternative solution. The aerial plant parts of the cranberry (Vaccinium macrocarpon) present a potential new source of antimicrobial secondary metabolites. Volatile essential oils were extracted from Stevens, Early Black, and Mullica Queen variety plants by steam distillation (SD) and the Clevenger method (CM), and their profiles were characterized by GC-MS. The extracts and two identified constituents, cinnamaldehyde and terpineol, were screened by the disc diffusion assay against Gram-positive B. cereus ATCC 11778 and S. aureus ATCC 25923 and Gram-negative bacteria E. coli ATCC 25922, P. aeruginosa ATCC 27853, and C. albicans ATCC 14053. Radical scavenging antioxidant activity was also determined using the DPPH assay. The CM extracts were rich in fatty acids, sesquiterpenes, and diterpenes, whereas the SD extracts contained more aldehydes, monoterpenes, and phenylpropanoids. All volatile extracts showed promising antioxidant activity; leaf extract activity was significantly higher than the vine (p < 0.05). The CM leaf and vine extracts exhibited antimicrobial activity against B. cereus, S. aureus, E. coli, and C. albicans compared to the SD, and the leaf extracts were more effective than the vine extracts. Individual constituents of leaf and vine extracts, cinnamaldehyde and alpha -terpineol, also showed antimicrobial activity against these organisms. The active constituents of the CM extracts are yet to be identified. A multivariate analysis revealed a particular pattern of inhibition of the tested organisms. Based on our results, cranberry volatile extracts have potential for future valorization as antibacterials, antifungals, and antioxidants.

Interactions between the gut microbiota and intestinal barrier may contribute to the pathophysiology of high-altitude illnesses. This study aimed to determine the effects of targeting the gut microbiota using dietary supplementation with a blend of fermentable fibers and polyphenol sources on gut microbiota composition, fecal short-chain fatty acids (SCFAs), and intestinal function and permeability during hypobaric hypoxia exposure. Healthy adults participated in a randomized, placebo-controlled, crossover study. Food products containing oligofructose-enriched inulin, galacto-oligosaccharide, high-amylose corn starch, cocoa, green tea and cranberry extracts, and blueberry powder (FP) or maltodextrin (placebo; PL) were consumed daily during three 2-wk phases separated by a >=1-wk washout. During the final 36 h of each phase, participants resided in a hypobaric chamber simulating low (LA; 500 m) or high (HA; 4,300 m) altitude creating three experimental conditions: PL + LA, PL + HA, and FP + HA. Twenty-six participants completed >=1 study phase and 13 [12 male; 21 +- 3 yr; body mass index (BMI) 25.4 +- 2.4 kg/m2] completed all three phases. Results demonstrated that FP mitigated hypoxia-induced increases in intestinal permeability within the small intestine and proximal colon while increasing Bifidobacterium relative abundance and decreasing gut microbiota alpha -diversity and colonic pH. Higher Bifidobacterium relative abundance and lower colonic pH were associated with greater reductions in intestinal permeability. However, FP did not alter fecal SCFA concentrations and increased gastrointestinal symptoms and altitude sickness during hypobaric hypoxia exposure. Findings suggest that targeting the gut microbiota with a combination of fermentable fibers and polyphenols can prevent hypobaric hypoxia-induced increases in intestinal permeability but that benefit does translate into a reduction in altitude illness symptoms.

OBJECTIVE: The antimicrobial efficacy of cranberry (CA) against oral infections was well evidenced. Influence of cranberry on the mechanical properties of heat-activated polymethyl methacrylate (HA-PMMA) denture base resin (DBR) is unexplored till date and is significant for a better understanding of the reinforcement. This study aimed to evaluate the flexural strength (FS), impact strength (IS), and surface microhardness (VHN) of heat-cure PMMA DBR reinforced with varying concentrations of Vaccinium macrocarpon (cranberry) extract. 

MATERIAL AND METHODS: A total of 150 samples were categorized into five groups (n = 10) by weight percentage of 0, 0.5, 1.0, 1.5, and 2.0 cranberry extract added into HA-PMMA polymer after the performance of antimicrobial efficacy testing of CA. Three-point bending test for FT, Izod impact testing for IS, and Vickers microhardness test were performed. Fractured sample surface was characterized by a high-resolution scanning electron microscope (HR-SEM). Raw data were statistically analyzed with one-way ANOVA and post hoc Bonferroni test. 

RESULTS: A significant improvement in flexural strength of 76.88 +/- 0.73 MPa, impact strength of 6.66 +/- 0.24 kJ/m2, and microhardness of 18.44 +/- 0.27 kg/mm2 was observed at 2 wt.% (p < 0.0001). Fractured surface topography showed dispersion of cranberry particles as a thin fibrous band intermeshed within resin matrix. 

CONCLUSIONS: Addition of up to 2 wt.% cranberry improved the FS, IS, and VHN on comparison to 0 wt.% control HA-PMMA.

The constant increase of bacterial resistance to antibiotics over time is an issue that requires finding therapeutic alternatives for the prevention and treatment of infections. Diabetes mellitus (DM) increases the predisposition to urinary tract infections (UTIs) through induced alterations in the urothelium secondary to high glucose concentrations and by affecting the immune response. Pharmacological formulas containing cranberry-derived compounds could represent a choice for the prophylaxis of UTIs in diabetics, but this possibility needs to be further analysed. Certain constituents of cranberry, especially polyphenols, have been shown to decrease bacterial adhesion to the urothelium, stimulate the secretion of Tamm-Horsfall protein, improve the integrity of the urothelium barrier and exert anti-inflammatory, antioxidant and antibacterial actions. The aim of this work is to evaluate potential pathogenetic mechanisms that could be interfered with by cranberry-derived compounds to prevent UTIs in diabetics.